Dr Martin Pall on XMRV

People do apparently, of their own volition, get well following CFS and go on to lead normal lives, what does this tell us about a virus based cause?/QUOTE]

I can't agree with you about this. The disease has unfortunately, and very wrongly, been used as a wastebasket diagnosis. Uninformed physicians sometimes declare anything they can't figure out to be 'CFS'. People who may feel unwell for any number of reasons, possibly with self-limiting, mono-like illnesses, have their illnesses resolve, and honestly think they had CFS and recovered.

I take issue with any theory that holds that people recover through their own will. Some very, very strong-willed, passionate people who have tried everything to get well, remain extremely sick.

We really don't know enough -- thanks to a quarter century of medical neglect -- to draw any such conclusions. It remains to be seen whether or not XMRV is causative and if people who were sick and recovered are positive for it, or not.

If XMRV is prevalent in a minimum of 3.5% of the population does that not make it a virulent virus,

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I'm not sure how you define virulent, but I would say no. 3.5% is not a huge number.

should we not therefore have seen or expect to see an explosion of cases mirrored in those showing symptoms of CFS?

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No. Getting the virus alone is not sufficient to induce CFS. You need other factors (all the docs have said this).

A German study found no XMRV in prostate cancer patients in their attempts to replicate the results which lead to the WPI study, what does this suggest about XMRV?

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That like many other pathogens (e.g. Cpn) the testing procedure is crucial. You have to use the correct assays.

People do apparently, of their own volition, get well following CFS and go on to lead normal lives, what does this tell us about a virus based cause?

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It means the virus itself can be controlled with a healthy immune-system.

If the answer to the above is that the virus goes dormant, as happens with herpes simplex for instance, then what changes bring this about and what keeps it dormant?

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A healthy immune system keeps it dormant. As to what changes bring this about, that is the $64,000 question.

People recover from chronic pathogen-induced disease all the time (e.g. lyme). What happens in these cases is not that every single virus/bacterium is killed, but rather that enough are killed that the immune system regains the upper hand and can keep any remaining pathogens at bay. Homoeostasis is restored.

The question of what causes viruses that are in the latent state to reactivate is a good one. I have studied this some for the case of the herpes family viruses, and my thoughts on that may be more general, perhaps applying to other viruses as well.

In order to make more virions, the DNA of the virus must be expressed as RNA, which in turn will code for the virus's proteins and make more of them. (If it's an RNA virus or specifically, a retrovirus, the RNA is first translated into DNA. In the case of a retrovirus, the virus's DNA is inserted into the human DNA.)

It is known that in general, methylation of DNA silences the gene it composes. So having an adequate methylation capacity would seem to be one way to block the propagation of viruses.

Once the DNA has been expressed as RNA, it goes to the ribosomes and starts putting together the virus's proteins. In the case of herpes family viruses, these proteins have a need for the amino acid arginine, and the amino acid lysine appears to substitute and cause problems if it is present in higher concentration. This appears to be the reason that taking L-lysine will counter cold sores, which are produced by the herpes simplex I virus. So raising the lysine to arginine ratio by diet and supplements is another strategy for countering at least the herpes family viruses.

Once the virus's proteins and DNA (or RNA, if it's an RNA virus) are available, the next step is to assemble them together. In herpes family viruses, there is a protein called glycoprotein B that forms the coat of the virion, and it must form disulfide bonds in order to do this. Disulfide bonds will not form in a chemically reducing environment. They need oxidizing conditions. The main substance that normally maintains reducing conditions in the cells is glutahione, which becomes depleted in CFS. So getting the glutathione level up is another way to block the propagation of at least herpes family viruses. I have heard that the formation of the coat on the XMRV virus also requires disulfide bond formation, so it seems that raising glutathione would be helpful for stopping this virus's propagation as well. This also applies to Chlamydia, which is an intracellular bacteria that is also latent and is found frequently in CFS. I suspect that mycoplasma, another bacteria, also need oxidizing conditions to thrive.

As you may know, methylation and glutathione are tied together in the sulfur metabolism. The simplified treatment approach for lifting the methylation cycle block has also been shown to raise glutathione. It therefore seems to me that one of the effects of this treatment would be to halt the propagation of viruses.

I will note also that the function of cell-mediated immunity, which is the type of immune response needed to control viral infections, requires methylation, glutathione, and a healthy folate metabolism (the latter is tied to the methylation cycle, also, and it is needed to make new human RNA and DNA for the propagation of lymphocytes in cell-mediated immunity).

So lifting the partial methylation cycle block should stop the propagation of the viruses, and it should also help the immune system to knock out the ones already present.

So those are my current thoughts on this issue. I hope they are helpful.

I realize that it may seem that I am simply trying to defend my GD-MCB hypothesis, but I actually believe that these arguments make sense.

Holmsey,
If you want to shake hands with the facts and clap em on the back, just go to the link I posted earlier on this thread. There I explained why Pall's central claim about XMRV was factually incorrect -- its not debatable, or even close, but I debated it anyway since I'm just such a sweetheart (of an acrid old crustacean).

There's no way his claim would be supported by any PhD or MD expert in infectious disease. I guarantee it. But youre right, this is not something terribly complex, and you can just look at the facts yourself if youre really the sly dog that you claim. And if you want to hear even more of them, I've got em on tap.

From what I know of him, I dont think hes a bad guy at all, I think hes an earnest researcher. Here he really missed the bus, but stuff happens. You dont even want to know about my little list of major peccadillos.

It is known that in general, methylation of DNA silences the gene it composes. So having an adequate methylation capacity would seem to be one way to block the propagation of viruses.
... getting the glutathione level up is another way to block the propagation of at least herpes family viruses. I have heard that the formation of the coat on the XMRV virus also requires disulfide bond formation, so it seems that raising glutathione would be helpful for stopping this virus's propagation as well. ...

As you may know, methylation and glutathione are tied together in the sulfur metabolism. The simplified treatment approach for lifting the methylation cycle block has also been shown to raise glutathione. It therefore seems to me that one of the effects of this treatment would be to halt the propagation of viruses.

I will note also that the function of cell-mediated immunity, which is the type of immune response needed to control viral infections, requires methylation, glutathione, and a healthy folate metabolism (the latter is tied to the methylation cycle, also, and it is needed to make new human RNA and DNA for the propagation of lymphocytes in cell-mediated immunity).

So lifting the partial methylation cycle block should stop the propagation of the viruses, and it should also help the immune system to knock out the ones already present.

...

I realize that it may seem that I am simply trying to defend my GD-MCB hypothesis, but I actually believe that these arguments make sense.

Best regards,

Rich

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Rich, I see nothing wrong with you defending the GD-MCB hypothesis, if that were your motivation here. And there is nothing wrong with Pall or others defending their theories, as long as they do their homework and do not make rash statements. Even WPI has a lot of defending to do also, if and when third-party researchers fail to produce the precise results WPI showed. I think there is a lot of premature excitement about XMRV, just wait, science is slow but deliberate, the debate will come.

I have thought for years the GD-MCB explanation was insufficient alone, something has to be upstream continually depleting the glutathione, because if the issue were just one of blockage then the micronutrients used in the simplified Yasko protocol would pretty much solve CFS for almost every case. And that does not happen, not even close.

But we need your theories Rich, as well as those of Pall, Teitelbaum, Gupta, and others. We are all like the blind men and the elephant, each showing one part of the beast. And the more blind men (or women) we have, the better will be our picture of CFS.

Will XMRV turn out to be the big picture, or just another blind man? That remains to be seen. I do know people who have recovered from serious CFS partly by boosting their glutathione (along with other treatments), so maybe Rich has a point. Cheney also has said he believes that managing our redox status may be critical in defending against something like XMRV.

People do apparently, of their own volition, get well following CFS and go on to lead normal lives, what does this tell us about a virus based cause?

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These people who get well "following CFS"--did they have CFS Fukuda, CFS Canadian Consensus, CFS Reeves Disease or CFS Simon's Disease? I agree with you that it is very unlikely that the people who get well "following" Reeves Disease or Simon's Disease have a virus-based cause.

But we need your theories Rich, as well as those of Pall, Teitelbaum, Gupta, and others. We are all like the blind men and the elephant, each showing one part of the beast. And the more blind men (or women) we have, the better will be our picture of CFS.

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It's hard to wait, I know. In the meantime, I hope we don't add to the difficulty of the scientific process by discrediting and discounting opinions that are not our own. I even hope (please don't shoot me) that we can find the energy to support the CDC as they try to replicate the XMRV studies in a different department. Encourage them to do it right this time. Send them thoughtful, constructive letters. Beg them to be a part of REAL science. Having the CDC at least trying to see the elephant will have impact worldwide.

I like this quote. I will need to remember it as more info about XMRV is discovered. I might not like all of it.

You either have science or you don't, and if you have it you are obliged to accept the surprising and disturbing pieces of information, even the overwhelming and upheaving ones, along with the neat and promptly useful bits. It is like that. Lewis Thomas

Many thanks for the direct replies concerning my questions. Bad choice of words, when I said own volition really I meant that it seems at least people do recover, whether through conscious or unconscious action. Certainly I have a friend who pushed his wife around in a wheelchair for almost two years, she then appeared to recover and has remained recovered since.
Annunziata, I know Im one of them, again apologies for my wording.
Fresh Eyes, Robin, you confirm that something happens, regardless of the cause, viral or otherwise, a change occurs in the overall condition.
Garcia, Im not a scientist Im an IT geek, and believe me 3.5% is a really, really, really big number when it refers to the world population. In the UK alone that would account for more than two and a quarter million people, how many do you think have had swine flu? I dont think the WHO will be making any plans soon to control that rate of infection. If the Germans have exercised poor science while WPI categorically have not thats something Id be interested in seeing the proofs for.
Richvank, thanks for this, it was reading the likes of this from people like Pall that had me reacting yesterday, assuming for now that there is a viral cause, and that cure isnt cure but dormancy, then clearly something brings that dormancy about, something alleviates at a chemical level the cause of symptoms, so why deride a microbiologist like Pall.
Eric, Im not suggesting that Pall isnt attached to his work, which is probably significant, but unlike many of those posting to this thread, who seem rabid in their determination that this is the TRUTH and all that went before should be crushed to dust, Im sure Pall will be more than accepting of any good science which follows this initial discovery.
Advocate, no offence was intended, Im sure theyre all well meaning caring individuals, I was simply trying to point out that Im sure Pall is as well. Regarding the rest that you say, all suggests its too early to jump to conclusions; we have a set of pretty compelling statistics which have already been disputed, which may be geographic. Even accepting the statistics, we have other virus present, and as far as I can tell, and Id really like to hear if its different, its only the statistics which support the theory that this is the cause of CFS rather than any other science. Who was it that said, there are lies, damn lies and statistics.
Gracenote, I certainly could not have said this better and it certainly reflects my own views.

Even accepting the statistics, we have other virus present, and as far as I can tell, and Id really like to hear if its different, its only the statistics which support the theory that this is the cause of CFS rather than any other science.

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These statistics are overwhelming. (I don't think you really mean to suggest that the finding of XMRV active and antibodies in almost all CFS patients and very very very few healthy controls is comparable to the finding of herpes family viruses in the majority of both CFS patients and healthy people is comparable, do you? That's the way this reads.)

Re: Statistics supporting a theory. Not sure how else anything is "proven" in science.

as far as I can tell, and Id really like to hear if its different, its only the statistics which support the theory that this is the cause of CFS rather than any other science.

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Actually I think it's a lot more than the statistics that have caused the WPI to feel so confident that XMRV is the key cause of CFS. I suspect the main reason for that confidence lies in the details of the nature of XMRV - a retrovirus that attacks the immune system - and in the unpublished details of their study of the behaviour of XMRV. For us, the best evidence that XMRV really is the key cause of CFS is the fact that the WPI have been prepared to put their reputations on the line and say that they're confident that it is.

Lots of other viruses have been (more weakly) associated with CFS, but this one is a retrovirus that disrupts/corrupts the immune system. Moreover its mechanisms of responding to cortisol, cytokines and hormones seem to make total sense with CFS patients' experience.

If you're looking for one single key that explains the entire complexity and diversity of CFS symptoms and unlocks the door for other viral infections, then a previously-unknown retrovirus that attacks the immune system would seem to be a pretty good candidate...

Many thanks for the direct replies concerning my questions. Bad choice of words, when I said ‘own volition’ really I meant that it seems at least people do recover, whether through conscious or unconscious action. Certainly I have a friend who pushed his wife around in a wheelchair for almost two years, she then appeared to recover and has remained ‘recovered’ since.
Annunziata, I know I’m one of them, again apologies for my wording.
Fresh Eyes, Robin, you confirm that something happens, regardless of the cause, viral or otherwise, a change occurs in the overall condition.
Garcia, I’m not a ‘scientist’ I’m an IT geek, and believe me 3.5% is a really, really, really big number when it refers to the world population. In the UK alone that would account for more than two and a quarter million people, how many do you think have had swine flu? I don’t think the WHO will be making any plans soon to control that rate of infection. If the Germans have exercised poor science while WPI categorically have not that’s something I’d be interested in seeing the proofs for.
Richvank, thanks for this, it was reading the likes of this from people like Pall that had me reacting yesterday, assuming for now that there is a viral cause, and that cure isn’t cure but dormancy, then clearly something brings that dormancy about, something alleviates at a chemical level the cause of symptoms, so why deride a microbiologist like Pall.
Eric, I’m not suggesting that Pall isn’t attached to his work, which is probably significant, but unlike many of those posting to this thread, who seem rabid in their determination that ‘this is the TRUTH’ and all that went before should be crushed to dust, I’m sure Pall will be more than accepting of any good science which follows this initial discovery.
Advocate, no offence was intended, I’m sure they’re all well meaning caring individuals, I was simply trying to point out that I’m sure Pall is as well. Regarding the rest that you say, all suggests it’s too early to jump to conclusions; we have a set of pretty compelling statistics which have already been disputed, which may be geographic. Even accepting the statistics, we have other virus present, and as far as I can tell, and I’d really like to hear if it’s different, it’s only the statistics which support the ‘theory’ that this is the cause of CFS rather than any other science. Who was it that said, there are lies, damn lies and statistics.
Gracenote, I certainly could not have said this better and it certainly reflects my own views.

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Having spoken to a couple well renowned Infectious Disease experts over here in the UK they are quite underwhelmed by the Science article and feel that the XMRV is likely to be a secondary phenomenom rather than the cause of the disease with routine NHS testing likely to be years away unless subsequent research proves more convincing. That being said I guess something has to be the cause of it all.

These statistics are overwhelming. (I don't think you really mean to suggest that the finding of XMRV active and antibodies in almost all CFS patients and very very very few healthy controls is comparable to the finding of herpes family viruses in the majority of both CFS patients and healthy people is comparable, do you? That's the way this reads.)

Re: Statistics supporting a theory. Not sure how else anything is "proven" in science.

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Overwhelming stats, yes from infinitesimally small data sets and from uncorroborated results, I'd like to get excited, I really would, I've nothing against the 'theory'. That theory is proven, generally, when results are repeated and cross checked, and they might prove to be right, all I'm suggesting is that there's no need to go disrespecting prior work just because someone's come up with something you prefer. Science isn't about preference, me I hope they're right, prove it tomorrow and give me a cure by a week Tuesday. In the mean time I think Pall has contributed with sound science and should be respected for that not branded an alternate practitioner because he's raised reasonable questions.

I agree, it does look like a great candidate and I can't wait to find out if it is 'the' answer. I like people taking good theories to task though, being forced to answer tough questions, or tough questions driving good science, it all helps to get to the truth.

Having spoken to a couple well renowned Infectious Disease experts over here in the UK they are quite underwhelmed by the Science article and feel that the XMRV is likely to be a secondary phenomenom rather than the cause of the disease with routine NHS testing likely to be years away unless subsequent research proves more convincing. That being said I guess something has to be the cause of it all.

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Sounds like you have some very useful contacts there Scavo! Perhaps you can encourage them to look at it again! Refer them to John Coffin's presentation at CFSAC, that's the most convincing statement so far for such people I reckon.

If they're underwhelmed by the study then that makes them pretty unusual from what I can gather - much of the scientific community seems to be going ape over it all, especially the top people in relevant areas like retrovirology and AIDS.

It doesn't really surprise me that these sort of people are sceptical that XMRV is the cause of CFS. Firstly because anybody who's deep enough inside the UK medical/scientific world knows as a rigid dogma that CFS is a psychological condition, so their immediate reaction is going to be that our depressive state and psychologically-weakened immune system has just opened the door to XMRV: that would be the automatic reaction of a conservative who believes that the existing 'science' and the authoritative view is usually right. Secondly because they aren't going to believe anything that comes out of a private US lab. Thirdly because - in the UK scientific world especially - people equate scepticism and conservatism with intelligence. The more sceptical you are, the more respected you are. We are trained from childhood to doubt everything. In my estimation, it takes a world-class education to create this level of ignorance. They won't believe anything until they're told it's OK to do so.

As for how long it will be before testing comes online, I spoke to my GP about it. He's not too bad really, but he's not at all a believer in CFS as a physical condition. His view was that, as soon as there is an independent study that confirms the WPI findings, things will suddenly move very quickly indeed. He said that once the results are confirmed, he would expect it to take about 3 months before the equipment was in place to start routine testing on the NHS. He said it would be a bit difficult in the current financial climate, but the costs of the new equipment required aren't really astronomical. And he added that if these results are correct, then the implications are so massive that they couldn't realistically be ignored.

Mark - yeah, I am quite lucky being a student as it means I just email people and pester virologists/microbiologists etc and fortunately they are really good at engaging, even if it's not with the answers I am looking for. With regards to your point about scepticism and conservatism, I think it's good to be cynical if you like when it comes to science but then I find myself stuck between being a med student and a CFS/ME sufferer - wanting to believe in the XMRV but at the same time thinking objectively about it all.

There are a couple major points that give me hope though and Dr Coffin is one of them, it's hard to argue with a world wide authority who really thinks we are going places with XMRV, that counts for a lot in my book. Secondly, from my reading with past false downs involving viruses it seems to centre upon what I would call ubiquitous critters - this fact separates XMRV from the crowd and is a source of much excitement for me, we really are looking at a different ball game. Lots more work to be done though but I think we are moving in the correct direction, hard not to jump fully aboard the bandwagon though !

Overwhelming stats, yes from infinitesimally small data sets and from uncorroborated results

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That's not quite as true as it appears at first glance; I'd encourage you and Scavo to keep digging and I think you'll find the evidence is much stronger than you believe. The data set for the published study was based (as I recall) on 300 people from 10 different groups including international samples. The results were the same in each of the 10 groups. The WPI study also included independent testing by two other labs, one of them being the US National Cancer Institute, and both labs confirmed the WPI results in detail. Those are the sort of details that led world-leading retrovirologist John Coffin to describe the study as exemplary and one of the best first studies he'd ever seen. A data set of 300 people may seem small, but for such studies as this I'm led to believe it's actually fairly large, and the detailed structure of how it was composed, and the compelling statistics that resulted, mean that the probabilities of major error are actually the 'infinitesimally small' numbers.

Even more important than that, though, are the unpublished findings. The Science study was actually due for publication back in May 09, but was delayed in order to make absolutely sure it was accepted by Science. Since then, the WPI have continued testing, studying and advising patients (I believe at least one poster in this forum has tested positive under Dr Peterson and wasn't part of the study, for example). So they have been testing for at least 6 months - unpublished as yet - and the figures of 95/97/98% on the antibody test are what they've mentioned in the press as their unpublished findings during that time. That must represent hundreds more positive results, and they've stated something along the lines that they haven't yet seen a single result that doesn't make sense.

OK, I have to admit, all the voices of scepticism are right, really: we do need further independent confirmation before we can scientifically say that these findings are 'proven' correct, and there will certainly be more twists and turns in the unfolding story. But if you dig away and find out more of what's beneath the surface, if you're a betting man I think it will be pretty obvious where to put your money. Recommend you start with the videos of Peterson and especially Coffin presenting to the CFSAC (please watch via the NIH site in order to boost the profile). They describe the XMRV phylogenetic tree, their analysis of the mutation rates of the XMRV genome in the samples, what all that implies, etc etc. There's not much room for doubt after you've digested all that stuff.

Scavo, thanks for your post. I don't know who you have spoken to in the NHS but they are idiots. But then I think that is a qualification for working in the NHS, so no real surprise there. I'm not sure how subsequent research could be any more convincing? You aren't going to get much higher than 95%. I'm looking for subsequent research to be much *less* convincing. Much less convincing, but still convincing will do it for me.

In medicine (and in the UK in particular) each field is much like a religion. If you go to a practitioner of that religion and contradict their dogma, or even bring them some new piece of information, they will not look kindly upon it.

Dr Burt Berkson says that Doctors are trained not educated. Trained like soldiers. Monkey see, monkey do. Education means being able to think for yourself. In medicine that is frowned upon.

Berkson himself tells of a time he was working in a hospital and was given two liver-failure patients (they had just eaten poisonous mushrooms) and told to look after them whilst they died. He had a contact in the NIH who he called and got some advice on using IV lipoic acid to counter the liver damage. He did this and promptly saved the patients lives against all the odds. Instead of being congratulated he was severely reprimanded and nearly got fired for not following orders!